The insulin receptor possesses tyrosine-specific protein kinase activity. Because this protein kinase is stimulated when insulin binds to the receptor, it has been proposed that the kinase activity plays a role in mediating insulin action. Using antibodies to pp60src, we have demonstrated that there is structural homology between the insulin receptor and the tyrosine kinase encoded by the src oncogene of Rous sarcoma virus. However, the insulin receptor gene does not appear to be the cellular proto-oncogene of any known viral oncogene. The question of the physiological significance of the receptor-associated kinase was addressed by searching for endogenous substrates which can be phosphorylated by the insulin receptor. Identification has been made of a glycoprotein (Mr = 120,000) in hepatic microsomes which is phosphorylated on tyrosine residues by the insulin receptor. The identity of this 120 kDa glycoprotein is not yet known. However, it is tempting to speculate that it may play a role in insulin action.